CA2673520A1 - Generation of oncolytic adenoviruses and uses thereof - Google Patents
Generation of oncolytic adenoviruses and uses thereof Download PDFInfo
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- CA2673520A1 CA2673520A1 CA002673520A CA2673520A CA2673520A1 CA 2673520 A1 CA2673520 A1 CA 2673520A1 CA 002673520 A CA002673520 A CA 002673520A CA 2673520 A CA2673520 A CA 2673520A CA 2673520 A1 CA2673520 A1 CA 2673520A1
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- adenovirus
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/13—Tumour cells, irrespective of tissue of origin
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10341—Use of virus, viral particle or viral elements as a vector
- C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10351—Methods of production or purification of viral material
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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Applications Claiming Priority (3)
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| US87662706P | 2006-12-22 | 2006-12-22 | |
| US60/876,627 | 2006-12-22 | ||
| PCT/US2007/088415 WO2008080003A2 (en) | 2006-12-22 | 2007-12-20 | Generation of oncolytic adenoviruses and uses thereof |
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| CA2673520A1 true CA2673520A1 (en) | 2008-07-03 |
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| CA002673520A Abandoned CA2673520A1 (en) | 2006-12-22 | 2007-12-20 | Generation of oncolytic adenoviruses and uses thereof |
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| US (1) | US8216819B2 (de) |
| EP (1) | EP2094284A2 (de) |
| JP (1) | JP5448840B2 (de) |
| CA (1) | CA2673520A1 (de) |
| WO (1) | WO2008080003A2 (de) |
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| CN112516179A (zh) * | 2013-06-14 | 2021-03-19 | 普赛奥克苏斯治疗公司 | 用于b型腺病毒的给药方案及制剂 |
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| KR101169109B1 (ko) | 2004-05-26 | 2012-07-26 | 싸이오서스 테라퓨틱스 엘티디. | 암 치료에 사용하기 위한 키메릭 아데노바이러스 |
| EP2670426B1 (de) | 2011-01-31 | 2017-05-10 | The General Hospital Corporation | Multimodale trail-moleküle und ihre verwendungen in zelltherapien |
| CN114262690A (zh) | 2011-04-15 | 2022-04-01 | 吉恩勒克斯公司 | 减毒的痘苗病毒的克隆毒株及其使用方法 |
| US8932607B2 (en) | 2012-03-12 | 2015-01-13 | Crucell Holland B.V. | Batches of recombinant adenovirus with altered terminal ends |
| AU2013231423B2 (en) * | 2012-03-12 | 2018-10-04 | Janssen Vaccines & Prevention B.V. | Batches of recombinant adenovirus with altered terminal ends |
| EP2877572B1 (de) | 2012-07-24 | 2018-11-28 | The General Hospital Corporation | Onkolytische virustherapie für resistente tumoren |
| US9605074B2 (en) | 2012-08-30 | 2017-03-28 | The General Hospital Corporation | Multifunctional nanobodies for treating cancer |
| SG11201506624SA (en) | 2013-02-28 | 2015-09-29 | Psioxus Therapuetics Ltd | A process for the production of adenovirus |
| PL2826856T3 (pl) * | 2013-07-16 | 2016-06-30 | Sia Latima | Genetycznie stabilny onkolityczny wirus RNA, sposób jego wytwarzania i zastosowanie |
| GB201322851D0 (en) * | 2013-12-23 | 2014-02-12 | Psioxus Therapeutics Ltd | Method |
| ES2661132T3 (es) | 2013-10-25 | 2018-03-27 | Psioxus Therapeutics Limited | Adenovirus oncolíticos armados con genes heterólogos |
| GB201415579D0 (en) * | 2014-09-03 | 2014-10-15 | Psioxus Therapeutics Ltd | A process |
| GB201406608D0 (en) | 2014-04-12 | 2014-05-28 | Psioxus Therapeutics Ltd | Virus |
| GB201510197D0 (en) | 2014-06-12 | 2015-07-29 | Psioxus Therapeutics Ltd | Method of treating ovarian cancer |
| JP2017529070A (ja) | 2014-08-27 | 2017-10-05 | サイオクサス セラピューティクス リミテッド | アデノウイルスの製造方法 |
| WO2016168601A1 (en) | 2015-04-17 | 2016-10-20 | Khalid Shah | Agents, systems and methods for treating cancer |
| DK3288573T3 (da) | 2015-04-30 | 2020-03-16 | Psioxus Therapeutics Ltd | Onkolytisk adenovirus, der koder for et b7-protein |
| MY193281A (en) | 2015-12-17 | 2022-09-30 | Psioxus Therapeutics Ltd | Group b adenovirus encoding an anti-tcr-complex antibody or fragment |
| WO2018041838A1 (en) | 2016-08-29 | 2018-03-08 | Psioxus Therapeutics Limited | Adenovirus armed with bispecific t cell engager (bite) |
| GB201713765D0 (en) | 2017-08-28 | 2017-10-11 | Psioxus Therapeutics Ltd | Modified adenovirus |
| WO2018083257A1 (en) | 2016-11-03 | 2018-05-11 | Psioxus Therapeutics Limited | Oncolytic adenovirus encoding transgenes |
| WO2018083258A1 (en) | 2016-11-03 | 2018-05-11 | Psioxus Therapeutics Limited | Oncolytic adenovirus encoding at least three transgenes |
| EP3630143B1 (de) | 2017-06-01 | 2023-06-07 | Akamis Bio Limited | Onkolytisches virus und verfahren |
| EP3679129A1 (de) | 2017-09-05 | 2020-07-15 | GLAdiator Biosciences, Inc. | Verfahren zur intrazellulären abgabe |
| WO2019191494A1 (en) * | 2018-03-28 | 2019-10-03 | Epicentrx, Inc. | Personalized cancer vaccines |
| GB201908933D0 (en) | 2019-06-21 | 2019-08-07 | Theolytics Ltd | Generation of diverse viral libraries |
| GB202009701D0 (en) | 2020-06-25 | 2020-08-12 | Theolytics Ltd | Generation of diverse viral libraries |
| GB202102049D0 (en) | 2021-02-13 | 2021-03-31 | Psioxus Therapeutics Ltd | Viruses |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7459153B2 (en) * | 2001-01-04 | 2008-12-02 | Wadell Goeran | Viral vectors for gene therapy |
| US7026164B2 (en) * | 2003-07-03 | 2006-04-11 | Cell Genesys, Inc. | Adenovirus packaging cell lines |
| KR101169109B1 (ko) * | 2004-05-26 | 2012-07-26 | 싸이오서스 테라퓨틱스 엘티디. | 암 치료에 사용하기 위한 키메릭 아데노바이러스 |
| US7550296B2 (en) * | 2004-12-01 | 2009-06-23 | Bayer Schering Pharma Ag | Generation of replication competent viruses for therapeutic use |
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- 2007-12-20 CA CA002673520A patent/CA2673520A1/en not_active Abandoned
- 2007-12-20 EP EP07869677A patent/EP2094284A2/de not_active Withdrawn
- 2007-12-20 US US12/520,538 patent/US8216819B2/en not_active Expired - Fee Related
- 2007-12-20 WO PCT/US2007/088415 patent/WO2008080003A2/en active Application Filing
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112516179A (zh) * | 2013-06-14 | 2021-03-19 | 普赛奥克苏斯治疗公司 | 用于b型腺病毒的给药方案及制剂 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008080003A2 (en) | 2008-07-03 |
| EP2094284A2 (de) | 2009-09-02 |
| JP5448840B2 (ja) | 2014-03-19 |
| US20100136658A1 (en) | 2010-06-03 |
| US8216819B2 (en) | 2012-07-10 |
| WO2008080003A3 (en) | 2008-12-24 |
| JP2010514418A (ja) | 2010-05-06 |
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